U.S. patent number 8,463,344 [Application Number 11/812,964] was granted by the patent office on 2013-06-11 for antigen monitoring system.
The grantee listed for this patent is Marlon Williams. Invention is credited to Marlon Williams.
United States Patent |
8,463,344 |
Williams |
June 11, 2013 |
Antigen monitoring system
Abstract
A method for detecting cancer in a subject includes
administering polysilicon mirrors to the subject, transmitting near
infrared light through subject's skin, receiving light which is
reflected from the polysilicon mirrors though the subject's skin,
converting received light into a digital signal and calculating a
level of CEA in the subject's blood from the digital signal.
Inventors: |
Williams; Marlon (Fort
Lauderdale, FL) |
Applicant: |
Name |
City |
State |
Country |
Type |
Williams; Marlon |
Fort Lauderdale |
FL |
US |
|
|
Family
ID: |
40137210 |
Appl.
No.: |
11/812,964 |
Filed: |
June 22, 2007 |
Prior Publication Data
|
|
|
|
Document
Identifier |
Publication Date |
|
US 20080319289 A1 |
Dec 25, 2008 |
|
Current U.S.
Class: |
600/322;
600/310 |
Current CPC
Class: |
C12Q
1/6886 (20130101); A61B 5/0059 (20130101) |
Current International
Class: |
A61B
5/1455 (20060101) |
Field of
Search: |
;600/310,322,473 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Winakur; Eric
Claims
What is claimed is:
1. A method for detecting or monitoring cancer in a subject,
comprising: administering polysilicon mirrors to random locations
within the bloodstream of a subject orally or by injection;
transmitting near infrared light through the subject's skin;
detecting light which is reflected from the polysilicon mirrors
though the subject's skin; converting received light into a digital
signal; and calculating a level of CEA in the subject's blood from
the digital signal.
2. The method of claim 1 wherein differences in the level of CEA in
a subject's blood are determined based on previously stored
measurements and currently taken measurements.
3. The method of claim 1 wherein the level of CEA is stored.
4. The method of claim 1 wherein the level of CEA is transmitted to
a third party.
5. The method of claim 4 wherein the level of CEA is transmitted to
the third party via an Internet.
6. The method of claim 1 wherein an intensity of light reflected
from said polysilicon mirrors varies according to an amount of
antigen markers in the subject's blood.
Description
FIELD OF THE INVENTION
The present invention relates to the wireless monitoring of antigen
levels in blood, particularly in the blood of colorectal cancer
patients. The present invention also relates to the monitoring of
other cancers with antigen markers in blood, for example
Ovarian/Cervix/Uterus-CA-125, Testicular-Alphafetaprotein,
Gastrointestinal/Pancreas-CA19-9.
BACKGROUND OF THE INVENTION
Colorectal Cancer (i.e., cancer of the Colon, Rectum, Anus,
Appendix) is the second leading cause of cancer deaths in the
United States. Only lung cancer claims more lives. This year, more
than 130,000 Americans will be diagnosed with colorectal cancer.
Similar statistics are reported for many European countries.
Certain types of cancer are associated with antigen markers in the
blood, which holds a potential for early diagnosis by detection or
monitoring of antigen levels. Examples of cancers and their
associate antigen markers are: prostate cancer--PSA; pancreatic
cancer--CA125; ovarian and uterine cancer--fetaprotein; breast and
lung cancer--.beta.dlh.
While cancer is generally more receptive to treatment if diagnosed
in the early stages, it can be difficult to detect in an early
stage. With the recent emergence of genetic expression profiling,
oncologist have broken down malignancies to their genetic profile
which will allow them to classify cancers into distinct categories.
Tissues sampled for such genetic expression profiling can be
studied for antigen markers associated with additional types of
cancers.
Existing methods of detecting and monitoring cancer are time
consuming and complex. For example, a patient must go to a
facility, such as his physician's office, to have blood drawn. The
blood is then sent to an on-site or off-site laboratory for
processing to determine amounts of antigen markers. Costly
equipment is generally required, and the overall process can take a
great deal of time. The time-consuming nature of this process
becomes particularly burdensome when a patient may return for
testing periodically, such as weekly or monthly. Further, the
invasive nature of blood tests is often a deterrent to
patients.
A "biomaterial" is a non-living material used in a medical device
which is intended to interact with biological systems. Such
materials may be relatively "bioinert", "biocompatible",
"bioactive" or "uresorbable", depending on their biological
response in vivo.
When silicon is deliberately riddled with nanometer-sized holes, it
becomes biocompatible and biodegradable, and will not be rejected
by the body and it will dissolve harmlessly over time. Silicon
chips have been implanted into the body before--for example in
cochlear implants that convert sounds into electrical signals and
feed them directly into the brain--but they had to be shielded from
body tissues and the bloodstream.
Porous silicon, or "Biosilicon.TM.", needs no such protection--its
only by-product is silicic acid, which is present in many common
foods and drinks. It can be crafted into orthopedic and electronic
structures and perform a variety of medical functions inside the
body automatically.
A Biosilicon implant could be crafted into temporary scaffolds or
pins that would promote bone healing and growth and then dissolve
into nothing. Alternatively, it could contain both a reservoir of
drugs and a tiny computer system to control timing and dosage. It
could even be used as an internal diagnostic device, transmitting
data about a patient through his or her skin and enabling a doctor
to fine-tune its drug-release program without the need for
surgery.
SUMMARY OF THE INVENTION
It is an object of the invention to provide method and device of
detecting the antigen level in a patient's blood stream.
According to an embodiment of the invention, a device for detecting
cancer in a subject is provided. The device may include an infrared
sensor for emitting near infrared light to penetrate the subject's
skin. The device may further include an analog to digital converter
for converting an analog signal from the infrared sensor to a
digital signal. The device may also include a microcontroller to
calculate a carcinoembryonic antigen (CEA) level in the subject's
blood stream.
According to another embodiment of the invention, the device may
further include a read-only memory for storing an output of the
microcontroller.
According to yet another embodiment of the invention, the device
may include a communication device for transmitting the output of
the microcontroller stored in the read-only memory to another
device. The communication device may be a cellular modem and may
communicate with another device via the Internet.
According to an embodiment of the invention, the microcontroller
may calculate a change in a CEA level in the subject's blood
stream. According to a further embodiment, the infrared sensor may
receive light reflected from polysilicon mirrors in the subject's
blood.
According to another embodiment of the invention, a method for
detecting cancer in a subject may include administering polysilicon
mirrors to the subject, transmitting near infrared light through
subject's skin, receiving light which is reflected from the
polysilicon mirrors though the subject's skin, converting received
light into a digital signal and calculating a level of CEA in the
subject's blood from the digital signal.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates an embodiment of a process utilizing the device
and method of the present invention.
FIGS. 2A-2C graphically illustrate the measured values over a
period of time.
DETAILED DESCRIPTION
As stated above, cancerous tissues are being studied to identify
antigen markers for many different types of cancers. As antigen
markers are extracted from the tissue samples and identified, the
present invention contemplates using them with a rule-based
software to create the intelligence mechanism for use with an
integrated circuit (referred to herein as an I3C) that merges
digital technology with bioinformatics to formulate a non-invasive
approach to cancer detection and management. In an embodiment of
the invention, the rule-based software is interfaced with digital
technology to alert a communication device such as a paging device,
which the patient keeps close by. Alternatively, or additionally,
the patient's physician or other care giver is notified through
various known methods of communication, either wireless or
wired.
In an embodiment of the invention, the communication device will be
interfaced and equipped with a Wide Area Network (WAN)
communication interface so that the patient is constantly within a
global-positioned fixed communication loop. In such an embodiment,
the only significant time that the patient will not be within this
fixed loop is during flight or in certain overseas areas. In these
cases, the patient is placed back in the loop when returning to WAN
portals. The communication device would then alert a network
database (for example via E-mail or Internet) at the physician or
caregiver's office of a possible recurrence of a particular
protein. In an alternative embodiment, the communication device
utilizes known cellular communication technology (similar to text
messaging) or known satellite communication technology.
According to an embodiment of the invention, the I3C is generally
the size of a commercially available PDA to enhance portability and
usability. Indeed, the present invention contemplates integrating
the I3C into existing PDA-type or cell phone devices. The I3C
comprises an integrated circuit including an application-specific
integrated circuit (ASIC) and a light source. An ASIC is an
integrated circuit customised for a particular use, rather than
intended for general-purpose use. The I3C also comprises a
transducer (with analog to digital conversion), two data
acquisition microcontrollers for performing arithmetic functions
and input/output, memory such as read only memory (ROM) for
information and data storage, and a WAN interface for data
transfer. When these electronic components are integrated into a
device, the device allows a sensor (incorporated into the ASIC) to
report an analog voltage proportional to a protein marker
concentration to a transducer. The transducer will convert this
voltage to a digital value. The memory receives the information and
stores it along with the time and date, either in analog or digital
form.
An exemplary embodiment of the invention discussed hereinafter
works with the antigen marker carcinoembryonic antigen (CEA) in the
patient's blood. It is to be understood, however, that the present
invention contemplates detecting and monitoring a variety of
antigen markers in a similar fashion as described below.
CEA is a lycoprotein involved in cell adhesion, and is normally
produced during fetal development. The production of CEA stops
before birth, and is therfore not usually present in the blood of
healthy adults, although levels are raised in heavy smokers. CEA
was first identified in 1965 by Phil Gold and Samuel O. Freedman in
human colon cancer tissue extracts. It was found that serum from
individuals with colorectal, gastric, pancreatic, lung, and breast
carcinomas had higher levels of CEA than healthy individuals. CEA
measurement is presently used to identify recurrences after
surgical resection of cancerous cells. Elevated CEA levels should
return to normal after surgical resection, and elevation of CEA
during follow-up can therefore be an indicator of cancer
recurrence. CEA levels may also be raised in some non-neoplastic
conditions like ulcerative colitis, pancreatitis, and
cirrhosis.
CEA and related genes make up the CEA family belonging to the
immunoglobin superfamily. In humans, the carcinoembryonic antigen
family consists of 29 genes, 18 of which are normally
expressed.
The I3C receives inputs from multiple in vivo porous silicon
mirrors (PSMs). The input includes at least one of a level of CEA
in a patient's blood and a change in level of CEA in a patient's
blood. PSMs are biodegradable surfaces that dissolve harmlessly
over a period of time in the body. They elicit a specific
biological response when in vivo, which results in formation of a
bond with certain living tissue. PSMs comprise of particles of
silicon etched with nano-scale patterns of pores making them
extremely efficient light reflectors. Certain PSMs have been
designed for early detection of initial incidence and recurrence of
cancers. This is achieved by an application of a selective process
of a tumor antibody such as CEA. In an embodiment of the invention,
the PSM's are contained in a capsule swallowed by the patient. In
another embodiment of the invention, immunoassays are placed into
etchings of the PSMs, which are then implanted just below the skin.
The implantable PSM is preferably approximately 5 mm wide and 0.5
mm thick. After implantation or other introduction into the
patient's bloodstream, PSM particles having CEA-specific
immunoassays bind to the CEA molecules. The porous silicon used in
the PSMs is biocompatible and biodegradable, and therefore causes
no side effects while in the body or after disintegration. Porous
silicon differs from non-porous silicon because it has been treated
under special acid conditions which make it porous. Once the
silicon becomes porous, it acts like a highly reflective mirror.
The PSMs eventually breakdown into silicic acid, which is said to
be harmless to the body.
The I3C includes and monitors this process, or detects amounts of
antigen markers in a patient's blood that bind to the PSMs, using a
light source and an associated light sensor. According to an
embodiment of the invention, the light source emits near infrared
light. Near infrared light is used because it can penetrate the
patient's skin to reach the PSMs. After the PSMs have reached the
patient's bloodstream, the patient places a portion of his body,
such as a finger, on the sensor and the light source is activated,
causing the near infrared light to reach the etched surfaces of the
PSM in the patient's blood to reflect the light. Intensity and/or
other characteristics of light reflected from the PSMs will vary
according to the amount of antigen markers in the patient's blood.
This is because the antigen markers will adhere to the PSMs and
interfere with light reflection, much in the same way that a layer
of less reflective substance (such as Vaseline) placed on a mirror
will alter the characteristics of ambient light from that mirror.
The present invention contemplates using other types of light
sources that can penetrate the dermis, paired with an appropriate
sensor.
Studying the change in reflectance cause by differing
concentrations of antigen marker in the blood identifies a formula
(.DELTA.x/.DELTA.t) that allows calculation of the amount of
antigen marker in a patient's blood, and therefore changes in the
amount of antigen marker in the patient's blood.
As illustrated in the exemplary embodiment of FIG. 1, sensor 20,
preferably a retroreflective photoelectric sensor, is provided. A
photoelectric sensor is a device used to detect the presence of an
object by using a light transmitter, in this case infrared, and a
photoelectric receiver. A retroreflective photoelectric places the
transmitter and receiver at the same location and uses a reflector
to bounce the light beam back from the transmitter to the receiver.
An object is sensed when the beam is interrupted and fails to reach
the receiver. A proximity-sensing arrangement is one in which the
transmitted radiation must reflect off of the object in order to
reach the receiver. In this mode, an object is detected when the
receiver sees the transmitted source rather than when it fails to
see it. The output of the retro-reflective photoelectric sensor 20
is analog signal that represents the amount of antigen marker that
has bound to the PSM. The sensor 20 will preferably emit up to 2.5
mm of near infrared light into the epidermis establishing a
proportional relationship between antigen in blood and antigen on
mirrors. The perpendicular refection then comes back to the
collector side of the transistor. NPN phototransistor is used in
this device because the intensity of the signal measurement out is
perpendicular and will have a higher amplification and the NPN
transistor collector allows for greater currents and faster more
accurate operation.
The output of the sensor 20 in the input to an operation amplifier
(op-amp) 22. The op-amp may perform signal conditioning of the
fluctuations of the reflection due to individual patient epidermis
differences. This is so that individual skin conditions do not mask
the antigen levels on the signal measurement out. The op-amp will
be programmed and set according to the reflection parameters of the
porous silicon mirrors on the signal measurement out with no
antigen in the blood and the lowest reflection with antigen in
blood of a patient in remission. Since the I3C is preferably a CMOS
(complimentary metal oxide semiconductor) circuit, the actual
voltage of the reflection with no antigen in blood will be
programmed in the op-amp as the input bias current. The lowest
voltage of the reflection of a patient in remission will be
programmed as the input offset voltage. The op-amp 22 may now use
the input bias current and the input offset voltage against the
incoming current (reflection) from the phototransistor to
compensate for the common mode rejection ratio (CMRR). The CMRR
will allow the op-amp 22 to toggle the reflection between the two
inputs to find the common mode signal. In the event that the op-amp
CMRR rejects the measurement (signal does not fall between the
average of the 2 set parameters), the device may alert the patient
to run the test again. This can compensate for the fluctuations of
the individual patient epidermis differences so that skin
conditions do not mask antigen levels on the signal measurement
out.
The output of the op-amp 22 is fed to the analog to digital
converter 24. The A/D converter 24 converts the buffered reflection
from the op-amp from an analog signal to a digital signal. A
proportional relationship between antigen concentration on the
mirrors and the intensity of signal measurement out may be
established. Analog perpendicular reflection was sent back to the
collector of the phototransistor, transferred to an operational
amplifier for buffering, and now has been sent to a transducer
which has converted the reflection from a voltage to a digital
number. This conversion process will be determined by a set of 256
preprogrammed discrete values which can be produced over a wide
range of voltages. The transducer can be preprogrammed with an
8-bit resolution, meaning it can encode an analog input to 1 in 256
different levels. The values will range from 0-255 depending on the
application.
Microcontrollers 26 and 28 enable the transfer of the newly
converted digital information to two data acquisition
microcontrollers for arithmetic functions which will determine the
results of the test, i.e., the antigen level in the patient's blood
stream. More specifically, the newly transferred value from the
transducer, which represents the amount of antigen in the body at
the present time, goes first to the address bus of the
microcontroller for primary/temporary storage before being
transferred to the control bus. The control bus can decode the
value and convert the information to a binary coded decimal (BCD).
The control bus may then transfer the binary coded value to the
arithmetic logic unit (ALU). The ALU of this microcontroller will
preferably be programmed to divide the BCD value by the number of
days since last physician visit. The resulting numerical value,
known as the slope of patient response (SOPR), is now transferred
to the data bus. The data bus receives the SOPR and holds it in a
RAM for the next set of instructions. Although two microprocessors
and an operational amplifier have been described in conjunction
with this embodiment, it should be understood that both arithmetic
functions can be programmed into one microprocessor and the signal
conditioning can be programmed into the transducer during the A-D
conversion process.
The SOPR is transferred to the address bus of the second data
acquisition microcontroller 28 for primary/temporary storage before
being transferred to the control bus. The control bus takes the
numerical SOPR value and decodes it into BCD before transferring it
to the ALU. The ALU now has the SOPR in binary form. The ALU on
this microcontroller will be programmed to divide the change in the
BCD value (antigen level) by the change in time
(.DELTA.x/.DELTA.t), also known as the DATD. The resulting
numerical value, known as the discrete approximation of time
differential, is now transferred to the data bus. The data bus
receives the DATD and holds it in RAM for the next set of
instructions.
Read-only memory (ROM) 30 stores the numerical DATD before being
transferred to the parallel EEPROM for storage. Preferably, there
will be 256 addressable memory locations programmed on this
integrated circuit to cover the ample amounts of samples physicians
may want. The DATD numerical value is transferred to the first set
of address ports on the integrated circuit. The address bus then
decodes the DATD back to BCD. The BCD is now transferred to the
data bus and stored in the (ROM) 30 until further instruction. The
ROM simply remembers what the outputs should be for any given 256
combinations of inputs.
Communication device 32 may be a wide area network 30 or other
communication device which is capable of communication, preferably
over the Internet. Once the information is transmitted to the
Internet, it can be received by any party, such as the patient's
doctor. Alternatively, the communication device may be a cellular
modem which would dial a third party, such as the physician, and
transmit the necessary information. As can be readily understood,
there are many available means of communicating this information to
a third party and this application is not intended to be limited to
any one method.
In a preferred embodiment, the DATD stored BCD amounts are
transferred via a cellular modem to a physician database for
analysis. The physician can now receive in, an email format, the
dates, times, and values of samples, for example. The physician now
takes the sum total of all samples taken and divides it by the
number of samples taken. The resulting numerical value is known as
the "Patient Rate Of Change."
The measurement taken by the I3C can also be used to determine a
discrete approximation of time differential, which measures the
average antigen level over time.
For example, if a patient's antigen measurements for the past 12
months have been 4, 4, 4, 6, 7, 2, 5, 5, 5, 8, 9, 10, the average
is the sum of these measurements (69) is be divided by the number
of measurements (12) to get the an average antigen level of 5.75.
In medical terms, the discrete approximation of time differential
is referred to as a differential amount of CEA in time allotted. In
an embodiment of the invention, the slope of patient response and
the differential amount of CEA in time allotted are communicated to
a physician or caretaker, for example via email or another suitable
communication protocol as discussed above. A physician or caretaker
receiving the information can determine whether the patient--s CEA
level is low, moderate, or elevated (symptomatic of cancer
recurrence).
FIGS. 2A-2C show differences in levels of CEA relative to what each
level means from a standpoint of recurrence and remission.
The entire disclosure of the patents and publications referred in
this application, if any, are hereby incorporated herein in
entirety by reference.
* * * * *